Wacker oxidations of olefins

In the course of examining the CAI effect of conformational restriction of the C3-side-chain, intermediate 24 was prepared. Shankar and co-workers (Shankar et al., 1996) demonstrated that 10, a key intermediate in the research synthesis could be accessed by Wacker oxidation of olefin 24 (Scheme 13.7). Additionally, an alternative chiral variant of the well-precedented addition of zinc enolates to imines was demonstrated. Treatment of the bromoacetate 25, derived from 8-phenylmenthol with zinc and sonication followed by imine addition afforded 26 in 55% yield with greater than 99% de. Ethyl magnesium promoted ring-closure followed by C3 alkylation with 28, intercepts the previously demonstrated route through formation of olefin 24 (Shankar et al., 1996). 

Fig. 4.37 PdCI2// /,/ /-dimethylacetamide system for Wacker oxidation of olefins.

Similar, fluorous palladium /i-dikctonatc complexes (27) have been employed for Wacker oxidation of olefins to the corresponding ketones in a biphasic system [27] (Scheme 3.10). 

Wacker oxidation of olefins to ketones catalyzed by palladium complexes is a well-known process which has been applied to numerous olefins [120]. However, selective oxidation of Cg-Cig a-olefins remains a challenge. Recently, Mortreux et al. have developed a new catalytic system for the quantitative and selective oxidation of higher a-olefins in an aqueous medium [121-123]. For example, 1-decene was oxidized to 2-decanone in 98% yield using PdS04/ H9PV6M06O40/CUSO4 as the catalyst in the presence of per(2,6-di-0-methyl)-j9-cyclodextrin, which probably played the role of a reverse phase transfer reagent [Eq. (22)]. 

This procedure is a useful alternative to Wacker oxidation of olefins to ketones. 

In [51], Wacker oxidation of olefins was studied in the presence of catalytic systems comprising water-soluble calixarenes (sulfonated and glycydylated derivatives), palladium salt, and copper salt. The presence of nonpolar cavities in these molecules enables binding nonpolar substrates and their transfer into the aqueous phase where the reaction takes place. The activity of these catalysts depends on the complementarity between the cavity size of the host molecule and the size of the guest molecule. Therefore, substrate selectivity was exhibited. For example, the addition of calixarene increased the reaction rate for linear 1-alkenes which size corresponded to the size of the calixarene cavity (1-hexene for calix[4]arene and 1-octene for calix[6]arene). The activity of catalytic system applied for the oxidation of substituted styrenes also depended on the ratio of the size of the substrate molecule and that of the calixarene cavity. 

Water is a moderately reactive nucleophile involved in several well-known catalytic cycles, such as hydroxycarbonylation and Wacker oxidation of olefins. Besides these, palladium, as many other late transition metals, is reactive in the water gas shift reaction (WGS reaction) (Scheme 3), which is a source of metal hydride complexes. Further transformations triggered by the WGS reaction are versatile. 

Wacker oxidation of olefins by palladium complexes involves water as the nucleophilic reagent. Depending on conditions, the oxidation of olefins by Pd(II) salts in the presence of water gives ketones or chlorohydrins. The enantioselective procedure leading to the latter involves chiral bidentate phosphines, either sulfonated or nonsulfonated (Scheme 83, L = sulfonated (f )-TolBINAP).f ... 

Water is so extensively used in catalytic oxidation reactions that usually this fact is regarded as a natural feature and remains unnoticed. Wacker oxidation of olefins by palladium complexes involves water as a nucleophilic reagent, and thus the whole Wacker-type chemistry, which has developed into a powerful and versatile method of organic synthesis, is derived from aqueous catalysis [178]. The role of the nature of the co-oxidant and the mechanism of deactivation of the palladium catalyst due to aggregation and growth of inactive metal particles were recently investigated, and such study may have relevance for other processes catalyzed by phosphine-less palladium catalysts [179]. 

Optically active, vicinal chlorohydrins can serve as building blocks in much the same capacity as epoxides, azido alcohols, or diols. Enantioselec-tive access to chlorohydrins such as 165 was made possible through Henry s discoveiy of a Pd-catalyzed interrupted Wacker oxidation of olefins (Equation 28) [136, 137]. The process employs tetrasulfonated BINAP 166 as a chiral ligand embedded within the bimetallic triketone complex 164 [136]. 

Another attractive commercial route to MEK is via direct oxidation of / -butenes (34—39) in a reaction analogous to the Wacker-Hoechst process for acetaldehyde production via ethylene oxidation. In the Wacker-Hoechst process the oxidation of olefins is conducted in an aqueous solution containing palladium and copper chlorides. However, unlike acetaldehyde production, / -butene oxidation has not proved commercially successflil because chlorinated butanones and butyraldehyde by-products form which both reduce yields and compHcate product purification, and also because titanium-lined equipment is required to withstand chloride corrosion. 

In 1974, Hegedus and coworkers reported the pa]ladium(II)-promoted addition of secondary amines to a-olefins by analogy to the Wacker oxidation of terminal olefins and the platinum(II) promoted variant described earlier. This transformation provided an early example of (formally) alkene hydroamination and a remarkably direct route to tertiary amines without the usual problems associated with the use of alkyl halide electrophiles. 

Cu(rr) compounds are frequently used in conjunction with Pd(I[) in the oxidation of olefins in the Wacker process. Their role has been viewed as that of catalyst for autoxidation of Pd metal back to Pd(II). Dozono and Shiba report the rate of oxidation of ethylene by a PdCl2-CuCl2 couple to be given by... 

One of the earliest use of cyclodextrins as inverse phase transfer agents was in the Wacker oxidation of higher olefins to methyl ketones [22] with [PdCU] + [CuCU] catalyst (Scheme 10.12). Already at that time it was discovered, that cyclodextrins not only transported the olefins into the aqueous phase but imposed a substrate-selectivity, too with Ckh olefins the yields decreased dramatically and 1-tetradecene was only slightly oxidized. 

The interest in palladium-based catalysts is due to the double bond oxyhydration capacity of palladium, unique among the noble metals, and well known from the Wacker process. Fuyimoto and Kunugi [119] report that palladium salts on active charcoal are excellent catalysts for the oxidation of olefins, particularly ethylene but the higher olefins as well. A selectivity of 89% with respect to acetone beside 10% aldehyde production is obtained at a conversion level of 27%, using excess water and a very low temperature (105°C). Careful analysis of the charcoal does not indicate that metal oxide impurities are of importance. 

In the case of certain diolefins, the palladium-carbon sigma-bonded complexes can be isolated and the stereochemistry of the addition with a variety of nucleophiles is trans (4, 5, 6). The stereochemistry of the addition-elimination reactions in the case of the monoolefins, because of the instability of the intermediate sigma-bonded complex, is not clear. It has been argued (7, 8, 9) that the chelating diolefins are atypical, and the stereochemical results cannot be extended to monoolefins since approach of an external nucleophile from the cis side presents steric problems. The trans stereochemistry has also been attributed either to the inability of the chelating diolefins to rotate 90° from the position perpendicular to the square plane of the metal complex to a position which would favor cis addition by metal and a ligand attached to it (10), or to the fact that methanol (nucleophile) does not coordinate to the metal prior to addition (11). In the Wacker Process, the kinetics of oxidation of olefins suggest, but do not require, the cis hydroxypalladation of olefins (12,13,14). The acetoxypalladation of a simple monoolefin, cyclohexene, proceeds by trans addition (15, 16). 

The key step in this category involves the oxidation of a coordinated substrate by a metal ion or an oxometal species (see later). Examples include the palladium(II)-catalyzed oxidation of olefins (Wacker process) and the oxidative dehydrogenation of alcohols, where the key steps are reactions (5) and (6), respectively. 

The oxidation of olefins to aldehydes using a palladium chloride-copper(II) chloride catalyst, the Wacker Process, is a well-established industrial reaction. The mechanism of this reaction has not been established in detail, but it most probably involves a cr-7r rearrangement... 

Ansari IA, Joyasawal S, Gupta MK et al (2005) Wacker oxidation of terminal olefins in a mixture of [bmim][BF4] and water. Tetrahedron Lett 46(44) 7507-7510... 

Intramolecular coordination is apparently responsible for most examples of regioselective Wacker oxidations of internal olefins, but electronic effects are also operating [28], specifically in acceptor-substituted olefins. Steric effects are currently not well explored [8], Recent theoretical studies on the mechanism of the Wacker and related reactions are available elsewhere [29, 30],... 

Acetals result from oxidative coupling of alcohols with electron-poor terminal olefins followed by a second, redox-neutral addition of alcohol [11-13]. Acrylonitrile (41) is converted to 3,3-dimethoxypropionitrile (42), an intermediate in the industrial synthesis of thiamin (vitamin Bl), by use of an alkyl nitrite oxidant [57]. A stereoselective acetalization was performed with methacrylates 43 to yield 44 with variable de [58]. Rare examples of intermolecular acetalization with nonactivated olefins are observed with chelating allyl and homoallyl amines and thioethers (45, give acetals 46) [46]. As opposed to intermolecular acetalizations, the intramolecular variety do not require activated olefins, but a suitable spatial relationship of hydroxy groups and the alkene[13]. Thus, Wacker oxidation of enediol 47 gave bicyclic acetal 48 as a precursor of a fluorinated analogue of the pheromone fron-talin[59]. 

The Pd(II) hinge in cage 2 can also participate in a chemical transformation. The catalytic Wacker-type oxidation of olefins took place when 8-nonen-l -ol (32) was heated for 5 h at 80 °C in the presence of cage 2 (5 mol%), giving 9-hydroxynonan-2-one (33)... 

Textbook chemistry (297,298) teaches that palladium is the preferred catalyst for aerobic oxidation of olefins. When water is the solvent, nucleophilic water addition to coordinated olefins is the key step in the so-called Wacker cycle. Wacker oxidation occurs regiospecifically because a carbonyl group is formed at that carbon atom of the double bond where the nucleophile in a Markovnikov-like addition would enter. The Wacker reaction thus yields methylketones from primary alkenes ... 

Historically the homolytic type of catalysis has been known and studied for a long time. The heterolytic catalysts represent a relatively recent innovation but, nevertheless, include important developments such as the Wacker process for the oxidation of olefins. Regardless of the mechanism involved, the most important characteristics of metal catalysts for effecting oxidation are the accessibility of several oxidation states as well as the accommodation of various coordination numbers, both of which are properties of transition metal complexes. 

The Wacker process, of course, gives highly selective oxidation of olefins to aldehydes or ketones (42) the function of the 02 is to reoxidize the catalyst, and again any formation of a dioxygen complex is incidental, although such a species could be involved in the reoxidation step. Reoxidation of Cu(I) to Cu(II)/Cu(III) by 02 appears to be involved in certain Cu-containing oxidase systems, for example, ascorbic-acid oxidase (43, 44). 

Interesting properties may also be obtained when using a mixed addenda system in the presence of a co-catalyst The best known system [34d] is the V-substituted phosphomolybdate in conjunction with Pd for the oxidation of olefins to carbonyl compounds. This is analogous to the Wacker oxidation process based on CUCI2 and Pd. Unlike the Wacker process, the HPA system works at very low chloride concentration, or even in its absence. In addition the HPA is more active and selective and less corrosive. Other examples of such two-component catalytic systems include TF /TP, PT /Pt ", Ru"7Ru ", Br 7Br" and l /h-... 

Among the most significant developments in the field of catalysis in recent years have been the discovery and elucidation of various new, and often novel, catalytic reactions of transition metal ions and coordination compounds 13, 34). Examples of such reactions are the hydrogenation of olefins catalyzed by complexes of ruthenium (36), rhodium (61), cobalt (52), platinum (3, 26, 81), and other metals the hydroformylation of olefins catalyzed by complexes of cobalt or rhodium (Oxo process) (6, 46, 62) the dimerization of ethylene (i, 23) and polymerization of dienes (15, 64, 65) catalyzed by complexes of rhodium double-bond migration in olefins catalyzed by complexes of rhodium (24,42), palladium (42), cobalt (67), platinum (3, 5, 26, 81), and other metals (27) the oxidation of olefins to aldehydes, ketones, and vinyl esters, catalyzed by palladium chloride (Wacker process) (47, 48, 49,... 

Among the several types of homogeneously catalyzed reactions, oxidation is perhaps the most relevant and applicable to chemical industry. The well-known Wacker oxidation of ethylene to ethylene oxide is the classic example, although this is not a true catalytic process since the palladium (II) ion becomes reduced to metallic palladium unless an oxygen carrier is present. Related to this is the commercial reaction of ethylene and acetic acid to form vinyl acetate, although the mechanism of this reaction does not seem to have yet been discussed publicly. Attempts to achieve selective oxidation of olefins or hydrocarbons heterogeneously do not seem very successful. 

Oxidation of Olefins to Carbonyl Compounds (Wacker Process)... 

Non-oxidative isomerizations often occur when olefinic compounds react with noble metal compounds, e. g., in Wacker oxidation of higher olefins. An example is found in the oxidation of 1-octene where octane-2-, 3-, and 4-ones are formed, in this example with an immobilized Pd" catalyst [130]. A plausible mechanism with a hydridorhodium species as catalytically active moiety has been described by Cramer [131]. 

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